Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) are two of the most debilitating neurologic diseases of adults, of unknown cause and without adequate treatment. Evidence exists that both may be due in part to a persistent virus infection an immune abnormality, or both. The purpose of this Center is to bring together basic scientists and academic neurologists with complementary skills to attack the fundamental problems of ALS and MS. Such a program must function at multiple levels. Basic studies employing tissue cultures or organotypic cultures may provide fundamental biologic clues. Animal model systems which faithfully reproduce elements of human ALS or MS and the complexities of mammalian disease will be of great usefulness. Finally, human studies which can build on the findings from the animal investigations or provide insights that can be pursued more fully in suitable animal models will be undertaken. The ultimate goal is to design and initiate human clinical trials based on firm evidence of disease mechanisms in ALS or MS. In-vitro and in-vivo models of CNS virus persistence and demyelination will be studied. Mechanisms of demyelination will be investigated in both the central and peripheral nervous system. Human studies will explore the abnormalities of the immune response in MS and search for the target within the CNS. Molecular biological, virological cellular and humeral immunological, neuropathological and clinical approaches will be employed. A central focus of this Center will be an ALS/MS Clinic where well characterized patients and appropriate controls can be studied. Such patients will contribute materials for the projects described and will participate in logical clinical trials of experimental therapy. The instruction of health professionals interested in this condition will be fostered. This Center Grant will provide the foundation for a program of breadth confronting the clinical problems of ALS and MS from diagnosis to rehabilitation. It will concurrently provide the scientific depth to hopefully unravel the mysteries of these diseases and lead to rational treatment or prevention.